tbuckley/cabot-search huggingface dataset:
Correction: Pik3ip1 Is a Negative Immune Regulator that Inhibits Antitumor T-Cell Immunity
Authors: Yichen Chen, Jun Wang, Xi Wang, Xinye Li, Jingjing Song, Juan Fang, Xiangqi Liu, Tao Liu, Dikan Wang, Qunxing Li, Shuqiong Wen, Da Ma, Juan Xia, Liqun Luo, Song Guo Zheng, Jun Cui, Gucheng Zeng, Lieping Chen, Bin Cheng, Zhi Wang
Journal: Clinical Cancer Research (2022)

In the original version of this article (1), errors exist in two figures: in Fig. 5H, the LT+mPik-Ext and KO+mPik-Ext DAPI stainings were switched while the merged images are correct, and in Fig. 7H, the flow cytometry dot plot of HCC Blood was also used as a representative dot plot of HCC TILs. These errors have been corrected in the latest online HTML and PDF versions of the article. The authors regret these errors.
Overcoming resistance to oncolytic virus M1 by targeting PI3K-γ in tumor-associated myeloid cells
Authors: Yang Liu, Cuiying Xu, Xiaoting Xiao, Yinting Chen, Xiaobo Wang, Wenfeng Liu, Yaqian Tan, Wenbo Zhu, Jun Hu, Jiankai Liang, Guangmei Yan, Yuan Lin, Jing Cai
Journal: Molecular Therapy (2022)

Oncolytic viruses (OVs) have become a category of promising anticancer immunotherapeutic agents over the last decade. However, the fact that many individuals fail to respond to OVs highlights the importance of defining the barely known immunosuppressive mechanisms that lead to treatment resistance. Here we found that the immunosuppression mediated by tumor-associated myeloid cells (TAMCs) directly quenches the antitumor effect of oncolytic virus M1 (OVM). OVM induces myeloid cells to migrate into tumors and strengthens their immunosuppressive phenotypes. Mechanically, tumor cells treated with OVM secrete interleukin-6 (IL-6) to activate the phosphatidylinositol 3-kinase (PI3K)-γ/Akt axis in TAMCs, promoting infiltration of TAMCs and aggravating their inhibition on cytotoxic CD8+ T lymphocytes. Pharmacologically targeting PI3K-γ relieves TAMC-mediated immunosuppression and enhances the efficacy of OVM. Additional treatment with immune checkpoint antibodies eradicates multiple refractory solid tumors and induces potent long-term antitumor immune memory. Our findings indicate that OVM functions as a double-edged sword in antitumor immunity and provide insights into the rationale for liberating T cell-mediated antitumor activity by abolishing TAMC-mediated immunosuppression. Oncolytic viruses (OVs) have become a category of promising anticancer immunotherapeutic agents over the last decade. However, the fact that many individuals fail to respond to OVs highlights the importance of defining the barely known immunosuppressive mechanisms that lead to treatment resistance. Here we found that the immunosuppression mediated by tumor-associated myeloid cells (TAMCs) directly quenches the antitumor effect of oncolytic virus M1 (OVM). OVM induces myeloid cells to migrate into tumors and strengthens their immunosuppressive phenotypes. Mechanically, tumor cells treated with OVM secrete interleukin-6 (IL-6) to activate the phosphatidylinositol 3-kinase (PI3K)-γ/Akt axis in TAMCs, promoting infiltration of TAMCs and aggravating their inhibition on cytotoxic CD8+ T lymphocytes. Pharmacologically targeting PI3K-γ relieves TAMC-mediated immunosuppression and enhances the efficacy of OVM. Additional treatment with immune checkpoint antibodies eradicates multiple refractory solid tumors and induces potent long-term antitumor immune memory. Our findings indicate that OVM functions as a double-edged sword in antitumor immunity and provide insights into the rationale for liberating T cell-mediated antitumor activity by abolishing TAMC-mediated immunosuppression.
Ann Robinson’s research reviews —12 May 2022
Authors: Ann Robinson
Journal: BMJ (2022)

Self-monitoring of blood pressure-better or notDuring the pandemic, awareness has increased that self-monitoring is both possible and preferable in many scenarios.But does it improve outcomes?This pre-covid, unblinded, randomised trial in England found that a diverse range of pregnant women with known chronic or gestational hypertension, who measured their own blood pressure and used telemonitoring to report back, showed no adjusted mean difference in their mean systolic blood pressure when it was subsequently measured in clinic compared with women who had usual care, in which their blood pressure was always measured by a healthcare professional in an antenatal clinic (blood pressure 133.8 mm Hg versus 133.6 mm Hg in those with chronic hypertension, and 137.6 mm Hg versus 137.2 mm Hg in those with gestational hypertension).No significant differences were seen in gestational age at birth or in any outcomes in the infant.The self-monitoring groups scored significantly higher in self-rated questionnaires to assess cognitive and emotional responses at 30 weeks of pregnancy and postnatally, although measures of anxiety and adherence to blood pressure monitoring at baseline or follow-up were the same across the board.The authors are rather downbeat in their conclusions, saying that self-monitoring didn't improve outcomes.But another way of looking at it is that women reliably kept an eye on their own blood pressure with professional backup, and that no harm was done.
Activity of AZD7442 (tixagevimab-cilgavimab) against Omicron SARS-CoV-2 in patients with hematologic malignancies
Authors: Robert Stuver, Gunjan L. Shah, Neha S. Korde, Lindsey E. Roeker, Anthony R. Mato, Connie L. Batlevi, David J. Chung, Sital Doddi, Lorenzo Falchi, Boglarka Gyurkocza, Audrey Hamilton, Ya-Hui Lin, Ann A. Jakubowski, Erel Joffe, Heather L. Landau, Richard J. Lin, Sham Mailankody, M. Lia Palomba, Jae H. Park, Miguel-Angel Perales, Doris M. Ponce, Lakshmi V. Ramanathan, Gilles A. Salles, Michael Scordo, Susan K. Seo, Urvi A. Shah, Eytan M. Stein, David Straus, Saad Z. Usmani, James W. Young, Andrew D. Zelenetz, Ariela Noy, Santosha A. Vardhana
Journal: Cancer Cell (2022)
Cytomegalovirus blood reactivation in COVID-19 critically ill patients: risk factors and impact on mortality
Authors: Ilenia Gatto, Emanuela Biagioni, Irene Coloretti, Carlotta Farinelli, Camilla Avoni, Valeria Caciagli, Stefano Busani, Mario Sarti, Monica Pecorari, William Gennari, Giovanni Guaraldi, Erica Franceschini, Marianna Meschiari, Cristina Mussini, Roberto Tonelli, Enrico Clini, Andrea Cossarizza, Massimo Girardis, Massimo Girardis, Alberto Andreotti, Emanuela Biagioni, Filippo Bondi, Stefano Busani, Giovanni Chierego, Marzia Scotti, Lucia Serio, Annamaria Ghirardini, Marco Sita, Stefano De Julis, Lara Donno, Lorenzo Dall’Ara, Fabrizio Di Salvo, Carlotta Farinelli, Laura Rinaldi, Ilaria Cavazzuti, Andrea Ghidoni, Antonio Buono, Elena Ferrari, Daniela Iseppi, Anna Maria Ardito, Irene Coloretti, Sophie Venturelli, Elena Munari, Martina Tosi, Erika Roat, Ilenia Gatto, Marco Sarti, Andrea Cossarizza, Caterina Bellinazzi, Rebecca Borella, Sara De Biasi, Anna De Gaetano, Lucia Fidanza, Lara Gibellini, Anna Iannone, Domenico Lo Tartaro, Marco Mattioli, Milena Nasi, Annamaria Paolini, Marcello Pinti, Cristina Mussini, Giovanni Guaraldi, Marianna Meschiari, Alessandro Cozzi-Lepri, Jovana Milic, Marianna Menozzi, Erica Franceschini, Gianluca Cuomo, Gabriella Orlando, Vanni Borghi, Antonella Santoro, Margherita Di Gaetano, Cinzia Puzzolante, Federica Carli, Andrea Bedini, Luca Corradi, Enrico Clini, Roberto Tonelli, Riccardo Fantini, Ivana Castaniere, Luca Tabbì, Giulia Bruzzi, Chiara Nani, Fabiana Trentacosti, Pierluigi Donatelli, Maria Rosaria Pellegrino, Linda Manicardi, Antonio Moretti, Morgana Vermi, Caterina Cerbone, Monica Pecorari, William Gennari, Antonella Grottola, Giulia Fregni Serpini
Journal: Intensive Care Medicine (2022)
Traction-assisted endoscopic full-thickness resection for a colonic submucosal tumor
Authors: Jun Li, Ming Shen, Yunlei Wei, Di Zhang, Feng Liu
Journal: Endoscopy (2022)

Endoscopic full-thickness resection (EFTR) has been demonstrated to be feasible and safe in treating colonic submucosal tumors [1]; however, the EFTR procedure is challenging. Adequate tension and good exposure of the tumor and the deep seromuscular layer are very important for safe and effective resection during colonic EFTR. Here we introduce a novel clip-with-spring device for internal traction during colonic EFTR. The device consists of a metal clip with a spring fixed between the claws ([Fig. 1]). This can be easily inserted through the channel and used at any location. The traction direction can be adjusted intraoperatively without withdrawing the endoscope.
Characterization of the interaction of nanobubble ultrasound contrast agents with human blood components
Authors: Michaela B. Cooley, Eric C. Abenojar, Dana Wegierak, Anirban Sen Gupta, Michael C. Kolios, Agata A. Exner
Journal: Bioactive Materials (2022)

Nanoscale ultrasound contrast agents, or nanobubbles, are being explored in preclinical applications ranging from vascular and cardiac imaging to targeted drug delivery in cancer. These sub-micron particles are approximately 10x smaller than clinically available microbubbles. This allows them to effectively traverse compromised physiological barriers and circulate for extended periods of time. While various aspects of nanobubble behavior have been previously examined, their behavior in human whole blood has not yet been explored. Accordingly, herein we examined, for the first time, the short and long-term effects of blood components on nanobubble acoustic response. We observed differences in the kinetics of backscatter from nanobubble suspensions in whole blood compared to bubbles in phosphate buffered saline (PBS), plasma, or red blood cell solutions (RBCs). Specifically, after introducing nanobubbles to fresh human whole blood, signal enhancement, or the magnitude of nonlinear ultrasound signal, gradually increased by 22.8 ± 13.1% throughout our experiment, with peak intensity reached within 145 s. In contrast, nanobubbles in PBS had a stable signal with negligible change in intensity (-1.7 ± 3.2%) over 8 min. Under the same conditions, microbubbles made with the same lipid formulation showed a -56.8 ± 6.1% decrease in enhancement in whole blood. Subsequent confocal, fluorescent, and scanning electron microscopy analysis revealed attachment of the nanobubbles to the surface of RBCs, suggesting that direct interactions, or hitchhiking, of nanobubbles on RBCs in the presence of plasma may be a possible mechanism for the observed effects. This phenomenon could be key to extending nanobubble circulation time and has broad implications in drug delivery, where RBC interaction with nanoparticles could be exploited to improve delivery efficiency.
Challenging the utility of polygenic scores for social science: Environmental confounding, downward causation, and unknown biology
Authors: Callie H. Burt
Journal: Behavioral and Brain Sciences (2022)

Abstract The sociogenomics revolution is upon us, we are told. Whether revolutionary or not, sociogenomics is poised to flourish given the ease of incorporating polygenic scores (or PGSs) as “genetic propensities” for complex traits into social science research. Pointing to evidence of ubiquitous heritability and the accessibility of genetic data, scholars have argued that social scientists not only have an opportunity but a duty to add PGSs to social science research. Social science research that ignores genetics is, some proponents argue, at best partial and likely scientifically flawed, misleading, and wasteful. Here, I challenge arguments about the value of genetics for social science and with it the claimed necessity of incorporating PGSs into social science models as measures of genetic influences. In so doing, I discuss the impracticability of distinguishing genetic influences from environmental influences because of non-causal gene–environment correlations, especially population stratification, familial confounding, and downward causation. I explain how environmental effects masquerade as genetic influences in PGSs, which undermines their raison d’être as measures of genetic propensity, especially for complex socially contingent behaviors that are the subject of sociogenomics. Additionally, I draw attention to the partial, unknown biology, while highlighting the persistence of an implicit, unavoidable reductionist genes versus environments approach. Leaving sociopolitical and ethical concerns aside, I argue that the potential scientific rewards of adding PGSs to social science are few and greatly overstated and the scientific costs, which include obscuring structural disadvantages and cultural influences, outweigh these meager benefits for most social science applications.
Cardiovascular Benefit of Continuous Positive Airway Pressure in Adults with Coronary Artery Disease and Obstructive Sleep Apnea without Excessive Sleepiness
Authors: Ali Azarbarzin, Andrey Zinchuk, Andrew Wellman, Gonzalo Labarca, Daniel Vena, Laura Gell, Ludovico Messineo, David P. White, Daniel J. Gottlieb, Susan Redline, Yüksel Peker, Scott A. Sands
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Randomized controlled trials of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) have not demonstrated protection against adverse cardiovascular outcomes. Recently, observational studies revealed that OSA-related cardiovascular risk is concentrated in patients with an elevated pulse rate response to respiratory events (ΔHR).
Simultaneous Detection of 2 Types of Malignancies in a Pediatric Patient on FDG PET/CT Led to Diagnosis of Li-Fraumeni Syndrome
Authors: Ying Kan, Yukun Si, Wei Wang, Jigang Yang
Journal: Clinical Nuclear Medicine (2022)

A 17-month-old girl underwent FDG PET/CT to evaluate a right adrenal lesion, which showed abnormal 18 F-FDG avidity. In addition, an unexpected lesion with mild 18 F-FDG uptake was noted in the right anterior thoracic wall. Pathology demonstrated adrenocortical carcinoma in the right adrenal and rhabdosarcoma in both the left forearm and right anterior thoracic wall. Gene analysis confirmed the diagnosis of Li-Fraumeni syndrome. The present case emphasized FDG PET/CT value of showing simultaneously multiple lesions in Li-Fraumeni syndrome, especially in the early stage without the gene analysis result.
Corrigendum to ‘High prevalence of hepatitis C infection among multidrug-resistant tuberculosis patients’ [J Hepatol 72 (2020) 1028–1029]
Authors: Kwonjune J. Seung, Molly F. Franke, Catherine Hewison, Helena Huerga, Uzma Khan, Carole D. Mitnick
Journal: Journal of Hepatology (2022)
UNC45A deficiency causes microvillus inclusion disease–like phenotype by impairing myosin VB–dependent apical trafficking
Authors: Rémi Duclaux-Loras, Corinne Lebreton, Jérémy Berthelet, Fabienne Charbit-Henrion, Ophelie Nicolle, Céline Revenu de Courtils, Stephanie Waich, Taras Valovka, Anis Khiat, Marion Rabant, Caroline Racine, Ida Chiara Guerrera, Júlia Baptista, Maxime M. Mahe, Michael W. Hess, Béatrice Durel, Nathalie Lefort, Céline Banal, Mélanie Parisot, Cecile Talbotec, Florence Lacaille, Emmanuelle Ecochard-Dugelay, Arzu Meltem Demir, Georg F. Vogel, Laurence Faivre, Astor Rodrigues, Darren Fowler, Andreas R. Janecke, Thomas Müller, Lukas A. Huber, Fernando Rodrigues-Lima, Frank M. Ruemmele, Holm H. Uhlig, Filippo Del Bene, Grégoire Michaux, Nadine Cerf-Bensussan, Marianna Parlato
Journal: Journal of Clinical Investigation (2022)

Variants in the UNC45A cochaperone have been recently associated with a syndrome combining diarrhea, cholestasis, deafness, and bone fragility. Yet the mechanism underlying intestinal failure in UNC45A deficiency remains unclear. Here, biallelic variants in UNC45A were identified by next-generation sequencing in 6 patients with congenital diarrhea. Corroborating in silico prediction, variants either abolished UNC45A expression or altered protein conformation. Myosin VB was identified by mass spectrometry as client of the UNC45A chaperone and was found misfolded in UNC45AKO Caco-2 cells. In keeping with impaired myosin VB function, UNC45AKO Caco-2 cells showed abnormal epithelial morphogenesis that was restored by full-length UNC45A, but not by mutant alleles. Patients and UNC45AKO 3D organoids displayed altered luminal development and microvillus inclusions, while 2D cultures revealed Rab11 and apical transporter mislocalization as well as sparse and disorganized microvilli. All those features resembled the subcellular abnormalities observed in duodenal biopsies from patients with microvillus inclusion disease. Finally, microvillus inclusions and shortened microvilli were evidenced in enterocytes from unc45a-deficient zebrafish. Taken together, our results provide evidence that UNC45A plays an essential role in epithelial morphogenesis through its cochaperone function of myosin VB and that UNC45A loss causes a variant of microvillus inclusion disease.
Bimekizumab Safety in Patients With Moderate to Severe Plaque Psoriasis
Authors: Kenneth B. Gordon, Richard G. Langley, Richard B. Warren, Yukari Okubo, Linda Stein Gold, Joseph F. Merola, Luke Peterson, Krista Wixted, Nancy Cross, Delphine Deherder, Diamant Thaçi
Journal: JAMA Dermatology (2022)

Psoriasis is a chronic disease requiring long-term management; understanding the long-term safety profiles of psoriasis treatments, such as bimekizumab, is important.To evaluate the 2-year safety profile of bimekizumab in patients with moderate to severe plaque psoriasis.Safety data were pooled from a cohort of patients from 4 phase 2 randomized clinical trials (BE ABLE 1, BE ABLE 2, PS0016, and PS0018) and 4 phase 3 randomized clinical trials (BE VIVID, BE READY, BE SURE, and BE BRIGHT) to include 2 years of study treatment. Data were obtained on adults with moderate to severe plaque psoriasis (Psoriasis Area and Severity Index level ≥12, ≥10% body surface area affected by psoriasis, and an Investigator's Global Assessment score ≥3 on a 5-point scale) who were eligible for systemic psoriasis therapy and/or phototherapy.Included patients received 1 or more doses of bimekizumab during the phase 2 or phase 3 trials.Treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAEs leading to treatment discontinuation are reported using exposure-adjusted incidence rates (EAIRs) per 100 person-years.A total of 1789 patients (1252 [70.0%] men; mean [SD] age, 45.2 [13.5] years) were treated with 1 or more doses of bimekizumab across the phase 2/3 trials and were included in these analyses; total bimekizumab exposure was 3109.7 person-years. TEAEs occurred at an EAIR of 202.4 per 100 person-years and did not increase with longer duration of bimekizumab exposure. The 3 most frequently reported TEAEs were nasopharyngitis (19.1 per 100 person-years; 95% CI, 17.4-20.9 per 100 person-years), oral candidiasis (12.6 per 100 person-years; 95% CI, 11.3-14.0 per 100 person-years), and upper respiratory tract infection (8.9 per 100 person-years; 95% CI, 7.8-10.1 per 100 person-years). Most oral candidiasis events were mild or moderate; 3 events led to discontinuation. The EAIRs of inflammatory bowel disease (0.1 per 100 person-years; 95% CI, 0.0-0.3 per 100 person-years), adjudicated suicidal ideation and behavior (0.0 per 100 person-years; 95% CI, 0.0-0.2 per 100 person-years), and adjudicated major adverse cardiac events (0.5 per 100 person-years; 95% CI, 0.3-0.8 per 100 person-years) were low.In these pooled analyses of data from a cohort of patients from 8 randomized clinical trials, bimekizumab was well tolerated aside from an increased incidence of mild to moderate oral candidiasis. No safety signals were observed compared with previous reports, and there was no increased risk of AEs with longer duration of bimekizumab exposure.
Estradiol suppresses psoriatic inflammation in mice by regulating neutrophil and macrophage functions
Authors: Akimasa Adachi, Tetsuya Honda, Gyohei Egawa, Shuto Kanameishi, Riko Takimoto, Toshiya Miyake, Md Razib Hossain, Mayumi Komine, Mamitaro Ohtsuki, Matthias Gunzer, Koichi Ikuta, Kenji Kabashima
Journal: Journal of Allergy and Clinical Immunology (2022)
Comparison of Outcomes of Abdominal Wall Reconstruction Performed by Surgical Fellows vs Faculty
Authors: Abbas M. Hassan, Malke Asaad, Nikhil R. Shah, Francesco M. Egro, Jun Liu, Renata S. Maricevich, Jesse C. Selber, Matthew M. Hanasono, Charles E. Butler
Journal: JAMA Network Open (2022)

Concern regarding surgical trainees' operative autonomy has increased in recent years, emphasizing patient safety and preparation for independent practice. Regarding abdominal wall reconstruction (AWR), long-term outcomes of fellow autonomy have yet to be delineated.To evaluate the long-term outcomes of AWRs performed by fellows and compare them with those of AWRs performed by assistant, associate, and senior-level professors.This retrospective cohort study included patients who underwent AWR for ventral hernias or repair of tumor resection defects at a 710-bed tertiary cancer center between March 1, 2005, and June 30, 2019. The analysis was conducted between January 2020 and December 2021.Academic rank of primary surgeon.The primary outcome was hernia recurrence. Secondary outcomes were surgical site occurrence, surgical site infection, length of hospital stay, unplanned return to the operating room, and 30-day readmission. Multivariable hierarchical models were constructed to identify predictive factors.Of 810 consecutive patients, 720 (mean [SD] age, 59.8 [11.5] years; 375 female [52.1%]) met the inclusion criteria. Mean (SD) body mass index was 31.4 (6.7), and mean (SD) follow-up time was 42 (29) months. Assistant professors performed the most AWRs (276 [38.3%]), followed by associate professors (169 [23.5%]), senior-level professors (157 [21.8%]), and microsurgical fellows (118 [16.4%]). Compared with fellows and more junior surgeons, senior-level professors tended to operate on significantly older patients (mean [SD] age, 59.9 [10.9] years; P = .03), more patients with obesity (103 [65.6%]; P = .003), and patients with larger defects (247.9 [216.0] cm; P < .001), parastomal hernias (27 [17.2%]; P = .001), or rectus muscle violation (53 [33.8%]; P = .03). No significant differences were found for hernia recurrence, surgical site occurrence, surgical site infection, 30-day readmission rates, or length of stay among the fellows and assistant, associate, and senior-level professors in adjusted models. Compared with fellows, assistant professors (OR, 0.22; 95% CI, 0.08-0.64) and senior-level professors (OR, 0.20; 95% CI, 0.06-0.69) had lower rates of unplanned return to the operating room.This cohort study provides evidence-based reassurance that providing fellows with autonomy in performing AWRs does not compromise long-term patient outcomes. These findings may incite efforts to increase appropriate surgical trainee autonomy, thereby empowering future generations of competent, independent surgeons.
Only Halfway There with Sudden Infant Death Syndrome
Authors: Richard D. Goldstein, Hannah C. Kinney, Alan E. Guttmacher
Journal: New England Journal of Medicine (2022)

Medicine promotes a logically inconsistent message regarding SIDS: authoritative statements imply that SIDS is a consequence of unsafe sleep in biologically normal children, but there is vague acknowledgment that important biologic factors are involved in these deaths.